Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress.

Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood‒brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-κB/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-κB/STAT3 signaling pathway.

Intertwin nuchal translucency difference predicts the chance of co-twin death after fetal reduction in dichorionic triplet pregnancies: a retrospective analysis study.

OBJECTIVES: To compare the clinical outcomes of different multifetal pregnancy reduction (MFPR) programs in dichorionic (DC) triplets, and explore the association between early ultrasound characteristics and co-twin death after potassium chloride (KCl) injection into one monochorionic (MC) twin. METHODS: We retrospectively reviewed the data of DC triplets who underwent MFPR at our center during 2012-2021. Patients were grouped as follows: intracardiac KCl injection into one MC twin (group A), intracardiac KCl injection into both MC twins simultaneously (group B), and reduction of the singleton fetus (group C) and pregnancy outcomes were compared. Logistic regression was used to determine whether ultrasound measurements at 11-13+6 weeks predicted co-twin death and the receiver operator characteristic (ROC) analysis was conducted to assess the predictive performance. RESULTS: Finally, we enrolled 184 patients. 153 cases were in group A, and 18, 13 cases were in group B and C respectively. Gestational age at the time of MFPR did not differ among the 3 groups (median: [Formula: see text] weeks). The survival rate was 89.6%, 88.9%, and 92.3% in group A, B, and C respectively, which was comparable among groups. Preterm birth was more common in group C (10/12, 83.3%). After KCl injection into one MC twin, co-twin death occurred in 86.3% cases (132/153) within 1 day; however, 3 patients had 2 live births each, with normal postnatal development. Intertwin nuchal translucency (NT) difference/discordance significantly predicted co-twin death within 1 day after MFPR, and the areas under the ROC curve were 0.694 and 0.689, respectively. CONCLUSIONS: For MFPR in DC triplet pregnancies, reduction of the MC twins results in less preterm birth, and women with KCl injection into either one or both MC twins had similar outcomes. Large intertwin NT difference/discordance was associated with co-twin death within 1 day after KCl injection into one of the MC twins.

Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice.

In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (Aß) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. More importantly, we also found a negative correlation between LINGO-1 and CB1R on GABAergic interneurons in the hippocampus of AD mice, while the anti-LINGO-1 antibody reversed this relationship. These results indicated that LINGO-1 plays an important role in the process of hippocampal neuron loss in AD mice and that antagonizing LINGO-1 can effectively prevent hippocampal neuron loss and promote AHN. The improvement in cognitive abilities may be attributed to the improvement in AHN, and in the numbers of GABAergic interneurons and CCK-GABAergic interneurons rich in CB1Rs in the hippocampus of AD mice induced by the anti-LINGO-1 antibody. Collectively, the double target effect (LINGO-1 and CB1R) initiated by the anti-LINGO-1 antibody may provide an important basis for the study of drugs for the prevention and treatment of AD in the future.

Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus.

BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2  = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.

When a vesicular placenta meets a live fetus: case report of twin pregnancy with a partial hydatidiform mole.

BACKGROUND: Hydatidiform moles exhibit a distinctive gross appearance of multiple vesicles in the placenta. The advances in cytogenetic technologies have helped uncover novel entities of hydatidiform moles and enabled elaborate diagnoses. However, management of a vesicular placenta with a coexistent live fetus poses a bigger challenge beyond hydatidiform moles. CASE PRESENTATION: A 33-year-old woman was referred to our department for suspected hydatidiform mole coexistent with a live fetus at 24 weeks' gestation. The patient had conceived through double embryo transplantation, and first-trimester ultrasonography displayed a single sac. Mid-trimester imaging findings of normal placenta parenchyma admixed with multiple vesicles and a single amniotic cavity with a fetus led to suspicion of a singleton partial molar pregnancy. After confirmation of a normal diploid by amniocentesis and close surveillance, the patient delivered a healthy neonate. Preliminary microscopic examination of the placenta failed to clarify the diagnosis until fluorescence in situ hybridization showed a majority of XXY sex chromosomes. The patient developed suspected choriocarcinoma and achieved remission for 5 months after chemotherapy, but relapsed with suspected intermediate trophoblastic tumor. CONCLUSION: We report a rare case of twin pregnancy comprising a partial mole and a normal fetus that resembled a singleton partial molar pregnancy. Individualized care is important in conditions where a vesicular placenta coexists with a fetus. We strongly recommend ancillary examinations in addition to traditional morphologic assessment in such cases.

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management.

BACKGROUND: Haemolytic disease of the foetus and newborn (HDFN) is the most common aetiology of haemolytic anaemia and hyperbilirubinaemia in foetuses and neonates. Studies on the distribution of antibodies that cause haemolytic disease of the foetus (HDF) in China are limited, and the effects of multiple antibodies on the severity of HDF need further evaluation. METHODS: An observational cohort study from January 2005 to December 2019 was conducted in two hospitals affiliated with Sun Yat-sen University. Maternal red cell alloimmunization was identified by the Guangzhou Blood Centre. In total, 268 pregnant woman-foetus pairs were divided into four groups according to the type of maternal alloantibodies: anti-D, anti-D combined with other antibodies, other single-antibody and other multiple antibodies. The obstetric history, antibody characteristics, incidence of severe HDF and foetal outcomes were collected and compared. Logistic regression analysis of the risk factors for HDF and survival analysis of the severe HDF-free interval were conducted. RESULTS: Anti-D was the most common cause of HDF, followed by anti-M. No anti-K- or isolated anti-c-associated HDF was found. The incidence of severe HDF was higher in the group with anti-D combined with other antibodies than in the group with anti-D alone (P = 0.025), but no significant difference was found in haemoglobin level and reticulocyte count in the anaemic foetuses between these two groups. Foetuses in the other single-antibody group had a lower reticulocyte count (P = 0.007), more IUTs (P = 0.007) and an earlier onset of severe HDF (P = 0.012). The maximum antibody titre was significantly lower in the other single-antibody group than in the anti-D group (P < 0.001). A high maternal antibody titre (P < 0.001), multiple affected pregnancies (P < 0.001) and other single-antibody (P = 0.042) were independent risk factors for HDF. A higher reticulocyte count (P = 0.041) was an independent risk factor for severe HDF in anaemia foetuses affected by Rh(D) alloimmunization. CONCLUSIONS: The distribution of HDF-associated antibodies in China is different from that in Western countries. Other single non-Rh(D) antibodies could increase the risk of HDF, and anti-D combined with other antibodies would not influence the severity of foetal anaemia compared with anti-D alone.

Exercise-induced Nitric Oxide Contributes to Spatial Memory and Hippocampal Capillaries in Rats.

Exercise has been argued to improve cognitive function in both humans and rodents. Angiogenesis significantly contributes to brain health, including cognition. The hippocampus is a crucial brain region for cognitive function. However, studies quantifying the capillary changes in the hippocampus after running exercise are lacking. Moreover, the molecular details underlying the effects of running exercise remain poorly understood. We show that endogenous nitric oxide contributes to the beneficial effects of running exercise on cognition and hippocampal capillaries. Four weeks of running exercise significantly improved spatial memory ability and increased the number of capillaries in the cornu ammonis 1 subfield and dentate gyrus of Sprague-Dawley rats. Running exercise also significantly increased nitric oxide synthase activity and nitric oxide content in the rat hippocampus. After blocking the synthesis of endogenous nitric oxide by lateral ventricular injection of NG-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, the protective effect of running exercise on spatial memory was eliminated. The protective effect of running exercise on angiogenesis in the cornu ammonis 1 subfield and dentate gyrus of rats was also absent after nitric oxide synthase inhibition. Therefore, during running excise, endogenous nitric oxide may contribute to regulating spatial memory ability and angiogenesis in cornu ammonis 1 subfield and dentate gyrus of the hippocampus.

Disruption of a Upf1-like helicase-encoding gene OsPLS2 triggers light-dependent premature leaf senescence in rice.

KEY MESSAGE: The OsPLS2 locus was isolated and cloned by map-based cloning that encodes a Upf1-like helicase. Disruption of OsPLS2 accelerated light-dependent leaf senescence in the rice mutant of ospls2. Leaf senescence is a very complex physiological process controlled by both genetic and environmental factors, however its underlying molecular mechanisms remain elusive. In this study, we report a novel Oryza sativa premature leaf senescence mutant (ospls2). Through map-based cloning, a G-to-A substitution was determined at the 1st nucleotide of the 13th intron in the OsPLS2 gene that encodes a Upf1-like helicase. This mutation prompts aberrant splicing of OsPLS2 messenger and consequent disruption of its full-length protein translation, suggesting a negative role of OsPLS2 in regulating leaf senescence. Wild-type rice accordingly displayed a progressive drop of OsPSL2 protein levels with age-dependent leaf senescence. Shading and light filtration studies showed that the ospls2 phenotype, which was characteristic of photo-oxidative stress and reactive oxygen species (ROS) accumulation, was an effect of irritation by light. When continuously exposed to far-red light, exogenous H2O2 and/or abscisic acid (ABA), the ospls2 mutant sustained hypersensitive leaf senescence. In consistence, light and ROS signal pathways in ospls2 were activated by down-regulation of phytochrome genes, and up-regulation of PHYTOCHROME-INTERACTING FACTORS (PIFs) and WRKY genes, all promoting leaf senescence. Together, these data indicated that OsPLS2 played an essential role in leaf senescence and its disruption triggered light-dependent leaf senescence in rice.

Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly.

BACKGROUND: Whole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus. RESULTS: A search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1. CONCLUSIONS: Our findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5' stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother's third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants.

A 22-bp deletion in OsPLS3 gene encoding a DUF266-containing protein is implicated in rice leaf senescence.

Key message The OsPLS3 locus was isolated by map-based cloning that encodes a DUF266-containing protein. OsPLS3 regulates the onset of leaf senescence in rice. Glycosyltransferases (GTs) are one of the most important enzyme groups required for the modification of plant secondary metabolites and play a crucial role in plant growth and development, however the biological functions of most GTs remain elusive. We reported here the identification and characterization of a novel Oryza sativa premature leaf senescence mutant (ospls3). Through map-based cloning strategy, we determined that 22-bp deletion in the OsPLS3 gene encoding a domain of unknown function 266 (DUF266)-containing protein, a member of GT14-like, underlies the premature leaf senescence phenotype in the ospls3 mutant. The OsPLS3 mRNA levels progressively declined with the age-dependent leaf senescence in wild-type rice, implying a negative role of OsPLS3 in regulating leaf senescence. Physiological analysis, and histochemical staining and transmission electron microscopy assays indicated that the ospls3 mutant accumulated higher levels of ethylene and reactive oxygen species than its wild type. Furthermore, the ospls3 mutant showed hypersensitivity to exogenous 1-aminocyclopropane-1-carboxylic acid, H2O2 and high level of cytokinins. Our results indicated that the DUF266-containing gene OsPLS3 plays an important role in the onset of leaf senescence, in part through cytokinin and ethylene signaling in rice.

Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array.

OBJECTIVE: To evaluate the incidence and characteristics of unusual twinning by using single nucleotide polymorphism (SNP) array to identify twin zygosity. METHODS: This study reviewed 386 twin pairs who were seen for prenatal or postnatal diagnosis and underwent SNP array to detect zygosity. RESULTS: The incidence of monozygotic (MZ) twins was 11.36% (25/220) in the assisted reproductive technology (ART)-conceived group. Monochorionic dizygotic twins represented 3 of 24 monochorionic ART-conceived twin pairs (3/24, 12.50%) but none in the spontaneous twin pairs. Among 4 single-embryo transfer twin pairs, 3 represented unusual twinning, including 2 MZ twin pairs with discordant karyotypes and 1 dizygotic twin pair of the same gender. Of the pregnancies with 2 or more embryos transferred, 7.77% (15/193) were MZ. Additionally, there was a dichorionic monozygotic twin pair with placental vascular anastomoses from a day-5 blastocyst transfer. CONCLUSION: Single nucleotide polymorphism array can provide zygosity diagnosis in addition to chromosomal copy number variation and uniparental disomy detection. ART twin pregnancies have a risk of unusual twinning, such as monochorionic dizygotic, single-embryo transfer twin pairs with discordant karyotypes or dizygotic, and dichorionic monozygotic with vascular anastomoses from day-5 transfer.

Chromosomal aberrations and CNVs in twin fetuses with cardiovascular anomalies: Comparison between monochorionic diamniotic and dichorionic diamniotic twins.

OBJECTIVE: To investigate the types of cardiovascular anomalies and the results of invasive prenatal diagnosis in twin fetuses. METHODS: A total of 298 fetuses in 149 twin pairs were enrolled, in which 1 or 2 fetuses of a twin pair had cardiovascular anomalies. Prenatal diagnosis was performed on 290 fetuses of 149 twin pairs, including 150 monochorionic diamniotic (MCDA) fetuses (79 pairs) and 140 dichorionic diamniotic (DCDA) fetuses (70 pairs). G-Banding karyotyping and/or chromosomal microarray analysis were performed. The types of cardiovascular anomalies and the results of prenatal diagnosis were analyzed. RESULTS: Fifty percent (79/158) fetuses in MCDA group and 52.1% (73/140) fetuses in DCDA group were diagnosed with cardiovascular anomalies by ultrasound. Primary cardiac structural defects such as septal defects and tetralogy of Fallot were more common in DCDA group than in MCDA group, while acardiac anomaly was the most common in MCDA group. Chromosomal aberrations were identified in 7.7% fetuses (11/142) of MCDA group and in 18.3% fetuses (22/120) of DCDA group by G-banding karyotyping. Except benign copy number variations (CNVs), 37 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 21.3% (32/150) fetuses of MCDA group and 47 CNVs (pathogenic, likely pathogenic, and variant of uncertain significance) and chromosomal aberrations were detected in 32.1% (45/140) fetuses of DCDA group by chromosomal microarray analysis. CONCLUSIONS: Most of cardiovascular anomalies were identified in one fetus of a twin pair no matter in MCDA or DCDA twin. Primary cardiac structural defects were more common in DCDA group. Monozygotic twins may have discordant phenotypes, karyotypes, and CNVs between 2 fetuses of each pair.

Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia.

OBJECTIVE: To elucidate the relationship between copy number variations (CNVs) detected by high-resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH). METHODS: This study involved 77 pregnancies with PFAs who underwent CMA. RESULTS: Chromosomal aberrations including pathogenic CNVs and variants of unknown significance were detected in 31.2% (24/77) of all cases by CMA and in 18.5% (12/65) in fetuses with normal karyotypes. The high detection rate of clinically significant CNVs was evident in fetuses with cerebellar hypoplasia (54.6%, 6/11), vermis hypoplasia (33.3%, 1/3), and Dandy-Walker malformation (25.0%, 3/12). Compare with fetuses without other anomalies, cases with CH and additional malformations had the higher CMA detection rate (33.3% vs 88.9%). Three cases of isolated unilateral CH with intact vermis and normal CMA result had normal outcomes. The deletion of 5p15, 6q terminal deletion, and X chromosome aberrations were the most frequent genetic defects associated with cerebellar hypoplasia. CONCLUSION: Among fetuses with PFA, those with cerebellar hypoplasia, vermis hypoplasia, or Dandy-Walker malformation are at the highest risk of clinically significant CNVs. Chromosomal microarray analysis revealed the most frequent chromosomal aberrations associated with CH.

Intrauterine phenotypic features associated with 16p11.2 recurrent microdeletions.

OBJECTIVE: To investigate the detection rate of 16p11.2 recurrent microdeletions in fetuses with abnormal ultrasound findings and determine the common abnormal ultrasound findings in fetuses carrying the deletion. METHODS: This study reviewed 2262 consecutive fetuses with abnormal ultrasound findings who underwent prenatal chromosomal microarray analysis between October 2014 and December 2016. Cases carrying the 16p11.2 recurrent microdeletion were further genetically analyzed, and their clinical features were reviewed. RESULTS: The 16p11.2 recurrent microdeletion was identified in 12 fetuses, who had skeletal malformations (5/12), cardiovascular malformations (4/12), or isolated ultrasound markers (3/12). Approximately 0.5% (12/2262) of the fetuses with abnormal ultrasound findings harbored the deletion. The 5 fetuses with skeletal malformations displayed vertebral defects, particularly in the hemivertebra and butterfly vertebra. The detection rate of the 16p11.2 recurrent microdeletion was statistically significant (P < .05) among fetuses with skeletal malformations (3.6%, 5/140), fetuses with cardiovascular malformations (1.1%, 4/367), and fetuses with isolated ultrasound markers (0.4%, 3/702). CONCLUSION: The most frequent ultrasound findings in fetuses with 16p11.2 recurrent microdeletions are skeletal malformations (particularly vertebral malformations), followed by cardiovascular malformations, and isolated ultrasound markers.

Discordant phenotypes in monozygotic twins with 16p11.2 microdeletions including the SH2B1 gene.

A 200∼240 kb SH2B1-containing deletion region on 16p11.2 is associated with early-onset obesity and developmental delay. Here, we describe monozygotic twin brothers with discordant clinical presentations. Intrauterine fetal growth restriction was present in both twins. Additionally, twin A exhibited coarctation of aorta, left ventricular noncompaction, atrial septal defect, pericardial effusion, left hydronephrosis, and moderate developmental delay, whereas twin B exhibited single umbilical artery. Chromosome microarray analysis was performed on both twins and their parents. An identical 244 kb microdeletion on 16p11.2 including 9 Refseq genes, including SH2B1, was identified in the twins. The novel findings in monozygotic twins may expand the phenotypic spectrum of 16p11.2 microdeletion. Further studies are needed to strengthen the correlation between genotypes and abnormal clinical features.

Discordant intrauterine transfusion in dichorionic twin pregnancy with Rh isoimmunization.

Discordant intrauterine transfusion (IUT) in twin pregnancy with Rh isoimmunization is uncommon and complicated. We report a gravida 3, para 2 woman with a dichorionic diamniotic (DCDA) twin pregnancy and two fetuses received discordant transfusions. Middle cerebral artery peak systolic velocity (MCA-PSV) was used to evaluate the anemic degree in each foetus. IUT was performed 3 times in twin A and 4 times in twin B to reverse foetal anaemia. Transfusions were distinct due to the different tolerance to IUT, and the procedure could be continued in one foetus even if the other one underwent complications. Two male babies were born at 36 weeks of gestation and were given different treatments after birth. Twins were subsequently healthy after 2 years of follow up. The discordant IUT was due to the different tolerance to transfusion in the DCDA twins. Zygosity is important for the management and treatment of haemolytic anaemia in twin pregnancies.

[Prenatal genetic analysis of two fetuses with Miller-Dieker syndrome].

OBJECTIVE: To perform molecular cytogenetic study on two fetuses with abnormal ultrasound findings and analyze their genotype-phenotype correlation. METHODS: G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on amniotic fluid cells from both fetuses and peripheral blood samples from their parents. Results of SNP array were analyzed with bioinformatics software. RESULTS: G-banded karyotyping failed to detect any abnormalities in both fetuses and their parents. SNP array detected a 2.484 Mb terminal deletion at 17p13.3 [arr[hg19] 17p13.3 (83 035-2 567 405)×1] in fetus 1 and a 3.295 Mb terminal deletion at 17p13.3p13.2 [arr[hg19] 17p13.3p13.2 (83 035- 3 377 560)×1] in fetus 2. Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Metaphase FISH performed on amniotic fluid cells confirmed the presence of 17p13.3 and 17p13.3p13.2 deletions detected by the SNP array, while metaphase FISH performed on the parents excluded any potential chromosome rearrangements. CONCLUSION: Abnormal ultrasound features for fetuses with MDS mainly include central nervous system anomalies. SNP array can efficiently detect 17p13.3 microdeletions underlying MDS, and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations for MDS.

Application of chromosomal microarray analysis in prenatal diagnosis of fetal growth restriction.

OBJECTIVE: To investigate the clinical value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of chromosomal abnormalities in fetal growth restriction (FGR) cases. METHOD: The ultrasound findings of 107 FGR cases subjected to invasive prenatal diagnostic testing from March 2013 to October 2015 were retrospectively reviewed. Karyotyping was performed in all cases, and CMA was performed in 80 cases. RESULTS: In our study, karyotype analysis identified chromosomal aberrations in 9.3% (10/107) of the cases, while CMA detected abnormalities in 18.8% (15/80) of the cases. CMA achieved a 11.4% detection rate of chromosomal abnormalities among FGR cases with a normal karyotype. Among 53 FGR cases without malformations, CMA increased (9.4%; 95%CI, 1.6%-17.3%) the detection rate of chromosomal abnormalities. CMA identified more chromosomal abnormalities (50.0%; 95%CI, 19.0%-81.0%) than karyotyping (30.0%; 95%CI, 7.0%-65.0%) among the cases diagnosed during the second trimester. Further, the detection rate in cases with asymmetric FGR was higher with CMA (33.3%; 95%CI, 10.0%-65.0%) than with karyotyping (16.7 %; 95%CI, 2.0%-48.0%). CONCLUSION: Our study highlights the added value of CMA compared with karyotyping in evaluation of asymmetric FGR cases diagnosed during the second trimester without sonographic anomalies. © 2016 John Wiley & Sons, Ltd.

[Prenatal genetic diagnosis for a fetus with atypical neurofibromatosis type 1 microdeletion].

OBJECTIVE: To analyze the correlation between atypical neurofibromatosis type 1(NF1) microdeletion and fetal phenotype. METHODS: Fetal blood sampling was carried out for a woman bearing a fetus with talipes equinovarus. G-banded karyotyping and single nucleotide polymorphism array (SNP-array) were performed on the fetal blood sample. Fluorescence in situ hybridization (FISH) was used to confirm the result of SNP array analysis. FISH assay was also carried out on peripheral blood specimens from the parents to ascertain the origin of mutation. RESULTS: The karyotype of fetus was found to be 46, XY by G-banding analysis. However, a 3.132 Mb microdeletion was detected in chromosome region 17q11.2 by SNP array, which overlaped with the region of NF1 microdeletion syndrome. Analyzing of the specimens from the fetus and its parents with FISH has confirmed it to be a de novo deletion. CONCLUSION: Talipes equinovarus may be an abnormal sonographic feature of fetus with atypical NF1 microdeletion which can be accurately diagnosed with SNP array.

Effects of long-term exercise on spatial learning, memory ability, and cortical capillaries in aged rats.

BACKGROUND: This study aimed to determine the effects of long-term running exercise on spatial learning, spatial memory, and cortical capillaries in aged rats. MATERIAL AND METHODS: Fourteen-month-old female and male Sprague-Dawley rats were randomly divided into an exercised group (EG) and a non-exercised group (NG). The EG rats were trained on treadmill running for 4 or 14 months. The NG rats were housed under identical conditions without running. Spatial learning and memory were assessed with the Morris water maze. The cortical capillary parameters were quantitatively investigated using immunohistochemical and stereological methods. RESULTS: The escaped latencies of the EG were significantly different from those of the NG in 18-month-old females and 28-month-old males (p<0.05). However, 28-month-old females and 18-month-old males showed no differences in escape latency between the EG and NG (p>0.05). In 28-month-old female rats, stereological techniques showed significant differences between the EG and NG in the cortical capillary volume (median, 22.55 vs. 11.42, p<0.05) and the cortical capillary surface area (median, 7474.13 vs. 3935.90, p<0.05). In 28-month-old male rats, the EG had a significantly longer total cortical capillary length (median, 530.35 vs. 156.27, p<0.05), significantly larger cortical capillary volume (median, 16.47 vs. 3.65, p<0.01), and a significantly larger cortical capillary total surface area (median, 7885.79 vs. 1957.16, p<0.01) compared with the NG group. CONCLUSIONS: These data demonstrate that exercise improved spatial learning, memory capacity and cortical capillaries in aged rats.